 |
PDBsum entry 3gyh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
 |
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
DNA binding protein/DNA
|
PDB id
|
|
|
|
3gyh
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
|
References listed in PDB file
|
|
|
Key reference
|
|
|
Title
|
|
Flipping of alkylated DNA damage bridges base and nucleotide excision repair.
|
|
|
Authors
|
|
J.L.Tubbs,
V.Latypov,
S.Kanugula,
A.Butt,
M.Melikishvili,
R.Kraehenbuehl,
O.Fleck,
A.Marriott,
A.J.Watson,
B.Verbeek,
G.Mcgown,
M.Thorncroft,
M.F.Santibanez-Koref,
C.Millington,
A.S.Arvai,
M.D.Kroeger,
L.A.Peterson,
D.M.Williams,
M.G.Fried,
G.P.Margison,
A.E.Pegg,
J.A.Tainer.
|
|
|
Ref.
|
|
Nature, 2009,
459,
808-813.
|
|
|
PubMed id
|
|
|
|
|
|
Abstract
|
|
|
Alkyltransferase-like proteins (ATLs) share functional motifs with the cancer
chemotherapy target O(6)-alkylguanine-DNA alkyltransferase (AGT) and
paradoxically protect cells from the biological effects of DNA alkylation
damage, despite lacking the reactive cysteine and alkyltransferase activity of
AGT. Here we determine Schizosaccharomyces pombe ATL structures without and with
damaged DNA containing the endogenous lesion O(6)-methylguanine or
cigarette-smoke-derived O(6)-4-(3-pyridyl)-4-oxobutylguanine. These results
reveal non-enzymatic DNA nucleotide flipping plus increased DNA distortion and
binding pocket size compared to AGT. Our analysis of lesion-binding site
conservation identifies new ATLs in sea anemone and ancestral archaea,
indicating that ATL interactions are ancestral to present-day repair pathways in
all domains of life. Genetic connections to mammalian XPG (also known as ERCC5)
and ERCC1 in S. pombe homologues Rad13 and Swi10 and biochemical interactions
with Escherichia coli UvrA and UvrC combined with structural results reveal that
ATLs sculpt alkylated DNA to create a genetic and structural intersection of
base damage processing with nucleotide excision repair.
|
|
|
|
|
|
|
